Human neutrophil defensin-1 binding increases histidine kinase activity of SaeS in Staphylococcus aureus

  • Biochem Biophys Rep. 2025 Mar 21:42:101982. doi: 10.1016/j.bbrep.2025.101982.
Zhengfei Qi  1  2  3 ,  Shuru Lin  4  3 ,  Quanxiang Yu  3 ,  Rui Ma  3 ,  Kexin Zhang  3 ,  Wenqi Jiang  3 ,  Shurong Chen  1  2  3 ,  Yilin Mai  3 ,  Qingshan Bill Fu  1  2  4  3
Affiliations
  • 1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. Shanghai Institute of Materia Medica, Zhongshan Institute for Drug Discovery, Chinese Academy of Sciences, Zhongshan, 528400, China.
  • 4. College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
PMID: 40207086 DOI: 10.1016/j.bbrep.2025.101982
Abstract

Human neutrophil defensin-1 (HNP-1) can specifically activate the SaeRS two-component system(TCS), which is essential for controlling virulence and immune evasion factors in Staphylococcus aureus. The reaction to HNP1 requires the transmembrane domain of SaeS (SaeS™), however the precise mechanism is yet unknown. In this work, we reconstructed the SaeS™ protein into bicelles and discovered that HNP1 can interact directly with SaeS™ using BiacoreT200, their binding significantly increases SaeS kinase activity and activated the SaeRS system subsequently. Staphylococcus aureus may exploit host-derived factors released by human immune cells to activate its two-component signal transduction system, thereby enhancing antimicrobial peptide resistance.

Keywords
Bicelles; HNP1; Kinase activity; SaeS™; Two-component system.
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